vvedenie v klinicheskuyu farmakologiyu

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30 let klinicheskoy farmakologii v rossii: dostijeniya i perspektivi vvedenie v klinicheskuyu farmakologiyu akademik ramn, zaslujenniy deyatel nauki rf, professor v.g. kukes edinstvennaya krasota, kotoruyu ya znayu,- eto zdorove g.geyne oxranyaet zdorove cheloveka vrach, a ego osnovnoe orujie v borbe s zabolevaniyami eto lekarstvo klinicheskaya farmakologiya- eto nauka, izuchayushaya deystvie lekarstvennix sredstv u cheloveka v 1962 godu vishla kniga b.e. votchala «ocherki klinicheskoy farmakologii» «tsel klinicheskoy farmakologii- nauchit vracha farmakologicheskomu mishleniyu u posteli bolnogo» v.v. zakusov «klinicheskaya farmakologiya» m.d. mashkovskiy «lekarstvennie sredstva» k.m. lakin: «dlya dostijeniya uspexa terapii neobxodimo nauchitsya upravlyat sudboy lekarstvennogo sredstva v organizme bolnogo» v 1974 godu vishlo pismo voz «klinicheskaya farmakologiya: zadachi, organizatsiya obslujivaniya, i podgotovka kadrov» dinamika kolichestva zaregistrirovannix ls 1960 1982 2004 1000 ls 3000 ls 20000 ls poyavlenie kf tolko kf razrabotala metodologiyu klinicheskix issledovaniy novix ls v 4 fazi i faza (10-100) pervoe primenenie preparata u cheloveka, otsenka toksichnosti i bezopasnosti, opredelenie …

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farmakokinetiku ls nejelatelnie lekarstvennie reaktsii vzaimodeystvie lekarstvennix sredstv lekarstvennie sredstva, vizivaet usilenie, oslablenie ili stabilizatsiyu filogeneticheski determinirovannix biologicheskix reaktsiy. spetsifichnost effekta ls obuslovleno ego vzaimodeystviem s kletochnimi strukturami, obladayushimi opredelennimi biologicheskimi svoystvami. farmakodinamika 1. ionnie kanali; 2. nespetsificheskie belki i lipidi 3. retseptori: membrannie (retseptori i – iii tipov); vnutrikletochnie (retseptori iv tipa); immunoglobulinovie; 4. fermenti 5. neorganicheskie soedineniya (hcl, metalli); 6. na chujerodnix organizmax (mikroorganizmi). rasshifrovani molekuli-misheni ls izucheni chetire tipa retseptorov 1 tip. retseptori-ionnie kanali (n- xolinoretseptor, gamk-retseptori i dr.); 2 tip. retseptori, sopryajennie s g-belkami (adrenoretseptori, dofaminovie retseptori i dr.); 3 tip. retseptori s tirozinkinaznoy aktivnostyu (retseptori insulina, predserdnogo na-ure- ticheskogo peptida, faktorov rosta i dr.); 4 tip. vnutrikletochnie retseptori (retseptori steroidnix gormonov). plazmaticheskaya membrana    pk g-belok adenilat- tsiklaza (ats) (gs:«+»; gi:«-») i tip ii tip iii tip iv tip gdpgtp fosfolipaza s (gp) ionnie kanali: ca2+, k+, na+, na+/h+, mg2+ (gs, gk, gi) …

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tagonist antagonist lobelin dobutamin insulin aldosteron ganglio- blokatori metoprolol ne izvestno spirono- lakton vsasivanie metabolizm vivedenie transpotreri lekarstvennix sredstv fermenti metabolizma lekarstvennix sredstv ls kf ustanovleno, chto kontsentratsiya ls v plazme zavisit ot … kukes v.g. 2003 geneticheskiy polimorfizm sovmestno primenyaemie ls geneticheskiy polimorfizm sovmestno primenyaemie ls osnovnimi fermentami sistemi biotransformatsii ls yavlyayutsya izofermenti tsitoxroma r-450, lokalizovannie v gepatotsitax ustanovlen vklad razlichnix izofermentov tsitoxroma r-450 v metabolizm ls kukes v.g. 2001 cyp3a4 cyp2d6 cyp2c9 cyp1a2 cyp2c19 40,1% 20,8% 15,8% 8,3% 8,2% cyp3a4 induktori ingibitori substrati rifampitsin barbiturati glyukokortikoidi karbamazepin fenilbutazon fenitoin zveroboy makrolidi protivogribkovie preparati (azoli) sok greypfruta fluoksetin dilitiazem tsimetidin blokatori medlennix kaltsievix kanalov statini spironolakton antigistaminnie ls mestnie anestetiki polovie gormoni substrati, induktori i ingibitori cyp3a4 po dannim genotipirovaniya v evropeyskoy i moskovskoy populyatsiyax viyavleni: 9 % - «medlennix» metabolizatorov cyp2d6 2 % - «medlennix» metabolizatorov cyp2a6 0 % - «medlennix» metabolizatorov cyp3a4 glikoprotein-r (p-gp) transporteri organicheskix anionov …

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dotvrashenie proniknoveniya v tsns i cherez platsentu v plod aktivnaya sekretsiya ls v jelch funktsii glikoproteina-r funktsiya transporterov organicheskix anionov- vivedenie gidrofilnix ls i metabolitov (statini, metotreksat i dr.) epiteliotsit proksimalnix pochechnix kanaltsev / gepatotsit krov mocha / jelch transporteri organicheskix anionov ls ls odnako, v otdelnix sluchayax povishenie kontsentratsii ls v plazme krovi nelzya bilo ob'yasnit imeyushimisya znaniyami. okazalos, chto i geneticheskie faktori mogut imet osnovnoe znachenie v ob'yasnenii etix yavleniy. klinicheskoe nablyudenie jenshina 62 let, stradayushaya postoyannoy formoy mertsatelnoy aritmii dlya profilaktiki tromboembolicheskix oslojneniy naznachen varfarin 5 mg/sutki cherez 3 dnya otmetila nosovoe krovotechenie, krovoxarkane, makrogematuriyu po rezultatam koagulogrammi mno- 8 pri isxodnom 1,2. kukes v.g., 2004 sinyachkovaya sip pri prieme varfarina klinicheskoe nablyudenie u bolnoy viyavleno: kukes v.g., 2004 varfarin metaboliziruetsya cyp2c9 ustanovlenno, chto bolnaya yavlyaetsya gomozigotoy po «medlennomu» allelyu cyp2c9*3 ugnetenie biotransformatsii varfarina povishenie kontsentratsii varfarina i snijenie kontsentratsii ego metabolita v plazme gemorragicheskiy sindrom vremya …

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ya farmakokinetika nejelatelnie lekarstvennie reaktsii farmakodinamika vzaimodeystvie lekarstvennix sredstv kf doljna obespechit effektivnost i bezopasnost farmakoterapii farmakogenetika farmakogenomika farmako- epidemiologiya farmako- ekonomika v sovremennom mire farmakoterapii net garantiy, est tolko vozmojnosti, kotorie zavisyat ot nashix znaniy i umeniy. nashi znaniya est summa togo, chemu mi nauchilis. kukes v.g. klinicheskaya farmakologiya podobna derevu, kak bi moshni i krepki ni bili ego korni, ego mojno vikorchevat za chas, no nujni godi, chtobi ono stalo plodonosit prezentatsiya powerpoint 50 i 60e godi xarakterizovalis burnim razvitiem ximicheskoy i farmatsevticheskoy promishlennosti, chto privelo k vibrosu na rinok tisyach aktivnix substantsiy. odnako, dlya prigotovlenii lekarstv, neobxodimo bilo dokazat ix bezopasnost i effektivnost. no kakaya struktura bila sposobna eto osushestvit. otvetom na etot vopros bilo pismo voz o razvitii novoy klinicheskoy spetsialnosti klinicheskaya farmakologiya. diagramma1 cyp2a6*1 cyp2a6*2 cyp2a6*3 0.95 0.03 0.02 diagramma2 cyp3a4*1a cyp3a4*1a; 100% 1 diagramma3 cyp2d6*1 cyp2d6*3 cyp2d6*4 cyp2d6*4; 21% cyp2d6*3; 9% cyp2d6*1; 70% 0.7 …

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30 let klinicheskoy farmakologii v rossii: dostijeniya i perspektivi vvedenie v klinicheskuyu farmakologiyu akademik ramn, zaslujenniy deyatel nauki rf, professor v.g. kukes edinstvennaya krasota, kotoruyu ya znayu,- eto zdorove g.geyne oxranyaet zdorove cheloveka vrach, a ego osnovnoe orujie v borbe s zabolevaniyami eto lekarstvo klinicheskaya farmakologiya- eto nauka, izuchayushaya deystvie lekarstvennix sredstv u cheloveka v 1962 godu vishla kniga b.e. votchala «ocherki klinicheskoy farmakologii» «tsel klinicheskoy farmakologii- nauchit vracha farmakologicheskomu mishleniyu u posteli bolnogo» v.v. zakusov «klinicheskaya farmakologiya» m.d. mashkovskiy «lekarstvennie sredstva» k.m. lakin: «dlya dostijeniya uspexa terapii neobxodimo nauchitsya upravlyat sudboy lekarstvennogo sredstva v or...

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